Acetyl cholinesterase (AChE) is an important and essential enzyme in the body, which is responsible for the degradation or hydrolysis of acetyl choline, the neurotransmitter molecule responsible for synaptic transmission. Inhibition of AChE can cause a sharp increase in acetyl choline levels, causing overstimulation of the cholinergic system at both central and peripheral sites, resulting in the visual toxic signs commonly referred to as cholinergic crisis. Organophorus agents, such as pesticides (paraoxon, methylparaoxon, etc.) and nerve agents (Sarin, Cyclosarin, Soman, Tabun, VX, etc) represent the bulk of the major AChE inhibitor threat agents. Historically, various compounds have been proposed from the class of compounds that possess the N-alkyl bis-quaternary pyridinium moiety as a charged species. As a charged species, there may be diminished ability to penetrate the blood-brain barrier and protect against organophosphate poisoning in the brain and central nervous system (CNS).
Therefore, the invention disclosed herein has identified certain non-charged oxime based AChE reactivators with improved blood-brain barrier penetration that may be effective at reactivation of nerve agent-inhibited AChE and protect against organophosphate poisoning both peripherally and in the CNS.